Inflammatory Bowel Disease of

the Elderly: A Wake-Up Call

Seymour Katz, MD, FACP, MACG, and Richard Feldstein, MD, MS

Dr. Katz serves as Clinical Professor of

Medicine at the New York University
School of Medicine in New York,
New York, and as an Attending
Gastroenterologist at North Shore
University HospitalLong Island Jewish
Medical Center in Manhasset, New York.
Dr. Feldstein is a gastroenterology fellow
at North Shore University HospitalLong
Island Jewish Medical Center.

Abstract: As the baby-boomer generation enters the ranks of the

elderly (defined as patients over 60 years of age), the increased
burden of managing older inflammatory bowel disease (IBD) patients
requires recognition of the impact of comorbid disease, polypharmacy, and surgical candidacy criteria. There is a surprisingly positive
response to newer therapies and surgery, provided that a distinction
is made between fit elderly and frail elderly patients. The former
group should not be denied access to the newer biologics, clinical
trials, or surgical alternatives on the basis of age alone. There is a
need for clinicians caring for elderly IBD patients to be cognizant of
the multiple and often disguised conditions contributing to disease

Address correspondence to:

Dr. Seymour Katz
1000 Northern Blvd.
Great Neck, NY 11021;
Tel: 516-466-2340; Fax: 516-829-6421;
E-mail: SeymourKatz@optonline.net;
Web: www.liclinical.com

management as well as the importance for careful allocation of

health resources.

Keywords
Inammatory bowel disease, elderly,
drug interactions

he prognosis of elderly patients with inammatory bowel

disease (IBD) has consistently improved, discounting
earlier reports that presumed more aggressive disease and
higher mortality. The recognition of a growing elderly IBD population (dened as >60 years of age) mandates a critical overview of
drug interactions, comorbid disease inuence, varied disease presentations, and risks of interventions, both diagnostic and therapeutic.1-4 The demands of the emerging baby-boomer population
will require a comprehensive review of health-related resources.
The prospects of reevaluating the elderly into t elderly, distinguished from frail elderly, will better qualify patients for more
aggressive therapy and/or entry into clinical trials, as opposed to
classication based solely on age. Also required will be an increase
in the attention given to training physicians in the biology of IBD
in the elderly, the recognition of drug-drug interactions, and the
coexistence of multiple comorbid diseases. The following clinical
characteristics of elderly IBD patients are stated in comparison
with the younger IBD population.

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Demographics
The incidence of Crohns disease (CD) in patients over
60 years of age is 4 of 100,000 patients per year, whereas
the incidence of ulcerative colitis (UC) in patients over
60 years of age is 68 of 100,000.1-3 In Europe, 810%
of UC/CD patients are over 60 years of age (M>F).2
Generally, one third of newly diagnosed cases of CD
occur in elderly patients (F:M, 2:1).4-6 Unfortunately,
60% of elderly patients with CD are initially misdiagnosed, as opposed to 15% of younger patients.7,8 A greater
delay usually exists in diagnosing the elderly: 6 years
compared to only 2 years in younger patients,9 though
there are conicting data regarding this observation.8
Overall, clinicians have greater diculty diagnosing IBD
in the elderly.
Differences of Clinical
Presentation in the Elderly
Elderly IBD patients are less likely to present with symptoms of abdominal pain, diarrhea, and anemia.8-10 More
frequent symptoms include weight loss, bleeding, fever,
and paradoxical constipation (with distal UC, which is
more common than pancolitis).11 Colonic CD is more
common than small-bowel or ileocolonic disease and has
a lower incidence of fever and strictures than small-bowel
disease.9,12,13 Elderly patients have a lower incidence of
IBD family history and, as expected, a greater incidence
of osteoporosis, but their incidence of extraintestinal IBD
manifestations is similar to that of younger patients.8,10,12,14
However, a disparity exists in the literature, with some
reports claiming that there is no dierence in disease
location.8,10,14,15
Differential Diagnoses in the Elderly
There is a greater percentage of infectious colitis and
IBD (38% and 41%, respectively) when bloody diarrhea is the presenting symptom.16 For example, Giardia,
Yersinia, Escherichia coli 0157:H7, Clostridium dicile,
Salmonella, Shigella, and Campylobacter are often suggested by a shorter duration of symptoms and are detectable within 12 weeks of fever.17 C. dicile represents a
signicant threat to the elderly. Ischemia is a possibility
in elderly patients with congestive heart failure (CHF),
peripheral vascular disease, diabetes mellitus, arrhythmias
(eg, atrial brillation), or hypovolemia. It is characterized by rapid onset and pain, but it is usually a selflimiting process. Diverticular disease with segmental
colitis involves an active inammation site adjacent
to (sigmoid) diverticulae.18 It is responsive to antibiotics/
5-aminosalicylates (5-ASAs) and easily confused with CD

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and neoplasia (eg, carcinoma, lymphoma) of the bowel.18

Radiation therapy (RT) for prostate cancer may present
with an active, often-resistant proctitis. RT for ovarian
or intra-abdominal neoplasia must always be considered
in the dierential of bloody diarrhea.19 Neoplasia of the
colon and rectum obviously plays a signicant role in this
age group. Drug-related colitis can involve nonsteroidal
anti-inammatory drugs (NSAIDs), estrogens, digitalis
medicines, gold, sodium phosphate enemas, and methyldopa. Colonoscopic biopsy remains the most useful
examination for distinguishing acute self-limited colitis
from chronic idiopathic IBD. The diagnosis of microscopic colitis (collagenous/lymphocytic) requires more
than 20 intra-epithelial lymphocytes/100 epithelial cells
or a collagen band of greater than 10 micra, both of which
occur predominately in males.20
Disease Course
Elderly IBD patients have indications for medical and
surgical interventions similar to those of younger IBD
patients.8-10 Although the rst IBD attack in elderly
patients may be severe and require surgery, a study
from Mayo Clinic showed lower surgical odds in CD
patients with advancing age (odds ratio=0.86, 95% condence interval, 0.750.91) but there was no association
with disease distribution or smoking, unlike UC.21 The
surgical rate in UC was correlated to age, extent of disease, smoking, and comorbid conditions.22-24 Two other
studies demonstrated a lower surgical rate in elderly
IBD patients.13,25
Overall, the elderly have a less severe disease course
with fewer relapses and hospitalizations in UC, but not
in CD.8,12 Eighty percent of elderly patients ultimately
respond to medical therapy.15,26 Nevertheless, there is a
higher mortality rate after a severe initial attack (in UC or
CD), often related to multiple comorbidities.
There are data supporting a lower recurrence rate in
CD.8 Generally, the initial mortality rate in elderly CD
patients is similar to that in younger patients. However,
the elderly have a higher mortality rate after 10 years of
CD, as would be expected with advancing age, and they
indeed have a higher mortality rate (F>M) after 25 years
of disease or if older than 40 years of age at diagnosis.27-32
Surgery
Ulcerative Colitis Surgery
Although a higher rate of earlier surgery occurs in the
elderly with severe pancolitis, the rate of surgery late
in disease course (>5 years) is greater in young IBD
patients.33 Predictors of poor outcome in the elderly
include urgent surgery and hypoalbuminemia, although

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age, sex, and disease extent do not appear to inuence

the outcome.21 Surprisingly, ileal-anal pouch surgery has
been successful in the elderly IBD population, provided
that the patient retains good anal sphincter function. Ileal
pouch-anal anastomosis pouch failure rates do not dier
between young and old IBD patients,34 though anal rectal
incontinence contraindicates pouch surgery. Dysplasia is
a more common indication for colectomy in the elderly
UC patient. Toxic megacolon occurs much less commonly, and rates of overall morbidity/mortality are lower.
The anastomotic leak rates are similar to those in younger
IBD patients undergoing surgery.35
Crohns Disease Surgery
The need for CD surgery occurs less frequently with disease onset late in life. The likelihood of requiring surgery
is two times greater with ileocolitis than with disease limited to the ileum or colon, and ileocolitis is complicated
by a greater postoperative recurrence rate.36 Elderly CD
patients have higher mortality rates and more perioperative problems.37 Disparate reports in the literature have
noted recurrence rates in the elderly after CD surgery
ranging anywhere from ve times greater to equal to the
recurrence rates in younger patients.38
Overall, surgical rates are usually the same and may
actually be lower in elderly IBD patients than in younger
IBD patients.12,13,25 The shorter time between onset of
symptoms and the rst abdominal surgery is presumed to
be related to the need for excluding malignancy.8,26,39-41
Understanding the impact of making diet and
lifestyle changes is crucial to the success of the elderly
patients IBD management. Elderly patients have a lower
caloric requirement, often with restrictive diets (eg, low
salt, sugar, fat) due to comorbidities. A low residue diet
is often advised with active disease or brostenosis, but
enteral nutrition is of limited use. Supplemental vitamin
D and calcium are necessary but often overlooked. Total
parenteral nutrition is not eective as a primary therapy
for UC or stulizing CD in this population, which often
takes less than 50% of their calculated energy requirements when hospitalized.42,43 Fish-oil supplements have
not been successful in the maintenance of remission.44
There have been little or no data on butyrate enema
therapy in the elderly, but its malodorous smell and dicult administration would lessen any potential ecacy.
Pharmacokinetics and Drug Interactions
in Elderly Patients With Inflammatory
Bowel Disease
Glucocorticosteroids
Although prednisone and prednisolone are metabolically interconvertible, prednisolone is the pharmaco-

logically active form and has a 37% decrease in drug

clearance (unbound) due to decreased renal and nonrenal functions (Table 1).45 Budesonide (Rhinocort/
Pulmicort, AstraZenca) undergoes systemic CYP3A4mediated metabolism, which occurs in the intestinal
wall and liver with a subsequent bioavailability reduction
of 1015%.46 It is unknown whether the half-life (2.8 h)
of the drug and its clearance is altered in elderly patients,
but its high clearance, dependent upon hepatic blood
ow, may provide greater bioavailability. Glucocorticosteroids (GCS) are associated with a greater number of
adverse events, particularly osteoporosis and mental status
changes, in elderly IBD patients.47,48
Coadministration of phenytoin, phenobarbital,
ephedrine, or rifampin accelerates GCS clearance and
lessens its activity.3,49-51 The elderly are especially prone to
hypertension, hypokalemia, hyperglycemia, and mental
status changes, including depression.47,48 Although recent
literature regarding the herbal supplement St. Johns Wort
(inducer of the CYP3A4 enzyme) has shown a lack of
pharmacokinetic interaction with prednisone, vigilance
is still warranted with concurrent usage in the elderly.52
Even when used as an enema, as much as 25% can be
absorbed (eg, 60 mg hydrocortisone acetate in an enema
corresponds to the absorption of 3 mg of prednisone).3 In
addition, when prescribing GCS, it is always important
to have an exit strategy (eg, use of immunomodulators or
retrial of high-dose 5-ASA).
5-Aminosalicylates
5-ASA has a half-life of 0.52 hours with a clearance range
of 300610 mL/min depending upon intestinal and
hepatic acetylation (Table 2). In the elderly, sulfasalazine
elimination is slower (t=13.7 h) and associated with
a decreased glomerular ltration rate (GFR) and renal
clearance of acetylated 5-ASA (an increase of 50% in
inactive acetylated metabolites in steady-state plasma
levels).53 Potential nephrotoxicity (interstitial nephritis)
may occur if there is decreased renal function.54 5-ASA
formulations, particularly olsalazine, may increase the
international normalized ratio (INR) and prothrombin
time when administered with warfarin.3,55 Elevated
6-thioguanine (6-TGN) metabolites of 6-mercaptopurine (6-MP)/azathioprine (AZA) may occur with 5-ASA,
particularly in a dose-dependent manner (ie, increased
6-TGN levels of 40% with a 2.0-g dose and a 70%
increase with a 4.0-g dose by a mechanism that is as yet
unknown).56 This combination of drugs may result in
myelotoxicity in a small percentage of patients (7.7%).
Paradoxically, IBD patients refractory to conventional
doses of 6-MP/AZA may benet from the elevated
6-TGN levels produced by the administration of
5-ASA.56 Also noted are subtherapeutic levels of car-

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Table 1. Glucocorticosteroid (GCS) Drug Interactions

Drug

Drug-Drug Interaction

Prednisone
Budesonide
M-prednisolone
Prednisolone
Dexamethasone

Aminoglutethimide: decreases levels/therapeutic eects

of GCS
Amphotericin: increases hypokalemic eects of
amphotericin B
Antacid: may decrease the absorption of GCS
Anticholinesterase: concurrent use can lead to profound
weakness in myasthenia gravis patients
Antidiabetic agents: may decrease hypoglycemic eects of
diabetic medications
Aprepitant: may increase serum levels/therapeutic eects
of GCS
Antifungal agents: may increase serum levels/therapeutic
eects of GCS
Barbiturates: may decrease levels/therapeutic eects of GCS
Bile acid sequestrants: may reduce absorption of GCS
Calcium channel blockers: may increase serum levels/
therapeutic eects of GCS
Cyclosporine: concurrent use may increase levels of
cyclosporine
Diuretics: hypokalemic eects may be increased
Estrogens: may increase serum levels/therapeutic eects
of GCS
Fluoroquinolones: concurrent use can increase risk of
tendinopathies (tendonitis, rupture), particularly in the
elderly
Isoniazid: decreased serum levels/therapeutic eects of GCS
Macrolides: may increase serum levels/therapeutic eects
of GCS
Neuromuscular-blocking agents: concurrent use increases
the risk of myopathy
NSAIDs: concurrent use may lead to increased incidence of
GI adverse eects
Rifamycin derivatives: may decrease the levels/therapeutic
eects of GCS
Salicylates: concurrent use may increase GI adverse eects
Thalidomide: concurrent use may increase the risk of toxic
epidermal necrolysis and DVT
Vaccine (dead organism): may decrease the eect of vaccines
Vaccine (live organism): may increase the risk of infection.
Usage of live vaccines is contraindicated in immunosuppressed patients
Warfarin: concurrent use may increase anticoagulant eects
Note: Corticosteroids interfere with calcium absorption.
St. Johns Wort may decrease corticosteroid levels.

Cytochrome
Association

Renal
Hepatic
Impairment Impairment

Substrate of
CYP3A4

Use
with
caution
uid
retention
may occur

Induces
CYP2C19,
3A4

Use with
caution
uid
retention
may occur

DVT=deep vein thrombosis; GI=gastrointestinal; NSAIDS=nonsteroidal anti-inflammatory drugs.

diac glycosides with concurrent 5-ASA derivatives.

Olsalazine can cause new diarrhea due to excessive ilealchloride secretion.3 There is a small (<5%) incidence of
mesalamine-induced exacerbation of UC, which may
respond to a drug holiday (ie, discontinuing the 5ASA and observing the eects).57
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Immunomodulators
When given with allopurinol, 6-MP/AZA increases
6-TGN levels, potentially to the point of myelotoxicity58
(Tables 3 and 4). If coadministered, the 6-MP dose must
be reduced to one third or one quarter of the standard
dose. However, at one center, allopurinol has also been

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Table 2. Aminosalicylate Drug Interactions

Drug

Drug-Drug Interaction

Aminosalicylates

5-ASA derivatives: may decrease the

metabolism of thiopurine analogs
(azathioprine, mercaptopurine,
thioguanine)

Cytochrome
Association
None

5-ASA derivatives: may decrease

the absorption of cardiac glycosides
(digitoxin, digoxin)

Renal Impairment
Use with caution
minimal change
nephropathy and
acute/chronic interstitial
nephritis have been
reported

Hepatic
Impairment
Use with caution

5-ASA=5-aminosalicylic acid.

Table 3. 6-Mercaptopurine (6-MP) Drug Interactions

Drug

Drug-Drug Interaction

6-MP

Allopurinol: may cause increased levels of mercaptopurine by inhibition

of xanthine oxidase; may potentiate eect of bone marrow suppression.
Aminosalicylates (olsalazine, mesalamine, sulfasalazine): may inhibit
thiopurine methyltransferase, increasing toxicity and causing leukopenia/
myelosuppression
Azathioprine: metabolized to mercaptopurine; concomitant use may
result in profound myelosuppression
Doxorubicin: synergistic liver toxicity with mercaptopurine in more than
50% of patients
Hepatotoxic drugs: any agent that could potentially alter the metabolic
function of the liver could produce higher drug levels and greater toxicities
from either mercaptopurine or 6-thioguanine
Warfarin: mercaptopurine inhibits the anticoagulation eect of warfarin
by an unknown mechanism

Renal
Impairment

Hepatic
Impairment

Dose should be
reduced to avoid
accumulation, but
specic guidelines
are not available

Dose should be
reduced to avoid
accumulation,
but specic
guidelines are not
available

Hemodialysis
removed; supplemental dosing is
usually required

Table 4. Azathioprine Drug Interactions

Drug

Drug-Drug Interaction

Renal Impairment

Azathioprine

Angiotensin-converting enzyme inhibitors: concomitant

therapy may induce anemia and severe leukopenia
Allopurinol: may increase serum levels of active metabolite
(mercaptopurine)
Aminosalicylates (olsalazine, mesalamine, sulfasalazine):
may inhibit thiopurine methyltransferase, increasing
toxicity and causing leukopenia/myelosuppression
Mercaptopurine: azathioprine is metabolized to
mercaptopurine; concomitant use may result in profound
myelosuppression
Warfarin: anticoagulant eect may be decreased

CrCl 1050 mL/minute:

administer 75% of normal dose
CrCl <10 mL/minute: administer 50% of normal dose

Hepatic
Impairment
Use with
caution in
patients with
hepatic
impairment

Hemodialysis: dialyzable (~45%

removed in 8 hours)
Administer dose posthemodialysis: CAPD eects are unknown;
CAVH eects are unknown

CAPD=continuous ambulatory peritoneal dialysis; CAVH=continuous arteriovenous hemofiltration; CrCl=creatinine clearance.

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Table 5. Methotrexate (MTX) Drug Interactions

Hepatic
Impairment

Drug

Drug-Drug Interaction

Renal Impairment

MTX

Acitretin: may enhance hepatotoxic eects

Cholestyramine: decreases levels of MTX
Corticosteroids: decrease MTX uptake into leukemic cells
Cyclosporine: concomitant administration may increase toxicity
of both
Hepatotoxic agents: may increase the risk of hepatotoxic reactions
(retinoids, sulfasalazine)
Mercaptopurine: concomitant administration may increase levels
NSAIDs: BM suppression, aplastic anemia, gastrointestinal toxicity
with concomitant therapy
Penicillins: increase MTX concentrations (due to renal tubular
secretion)
Probenecid: increases MTX concentrations (due to in renal tubular
secretion)
Salicylates: may increase serum concentration of MTX
Sulfonamides: may increase MTX concentrations (due to in renal
tubular secretion); may folate levels increasing the risk/severity of
BM suppression
Tetracyclines: may increase MTX toxicity
Theophylline: MTX may increase theophylline levels

Elimination with renal Use caution with

impairment; may
preexisting liver
require dose reduction/
impairment
discontinuation
Bilirubin
CrCl 6180 mL/minute: 3.15 mg/dL or
reduce dose to 75%
AST >180 units:
CrCl 5160 mL/minute: administer 75%
reduce dose to 70%
of dose
CrCl 1050 mL/minute:
reduce dose to 3050% Bilirubin
CrCl <10 mL/minute:
>5 mg/dL:
avoid use
Do not use
Hemodialysis: Not
dialyzable (05%)

AST=aspartate aminotransferase; BM=bone marrow; CrCl=creatinine clearance; NSAIDS=nonsteroidal anti-inflammatory drugs.

used in patients with high thiopurine methyltransferase

activity and nonresponse to thiopurines by increasing
6-TGN levels with improved liver function tests.58,59
It should be emphasized that the combination of
6-MP and clotrimazole worsens leukopenia, angiotensin-converting enzyme inhibitors with 6-MP can induce
anemia and leukopenia, and 6-MP/AZA decreases the
anticoagulant eect of warfarin.3
Methotrexate
As methotrexate (MTX) is dependant on renal excretion,
decreased GFR impacts drug clearance (Table 5).3,60,61
NSAIDs/5-ASA inhibit renal tubular MTX excretion with
the expected increase in toxicity.3,61-64 Tetracycline inhibits
intestinal absorption of MTX, and penicillin decreases its
renal clearance.3,61,64,65 MTX alters theophylline clearance
and has the potential for bone marrow suppression and
hepatic brosis.3 Folate deciency worsens MTX toxicity,
therefore requiring supplemental folic acid.3
Cyclosporine
Cyclosporine (CSA) is metabolized by CYP3A4 (Table 6).
No age dierences in peak plasma concentration or
half-life (10.712.7 h) have been known to be reported.66
CSA may induce nephrotoxicity when given with antibiotics (eg, gentamicin, tobramycin, vancomycin, ketoconazole, trimethoprim/sulfamethoxazole, ciprooxacin), histamine-2-receptor antagonists (eg, cimeti342

Gastroenterology & Hepatology Volume 4, Issue 5 May 2008

dine), NSAIDs (eg, diclofenac), or melphalan (Alkeran,

GlaxoSmithKline).3,64,66,67 P-450 cytochrome inhibitors
decrease CSA metabolism with the increase of CSA
levels accompanied by the use of diltiazem, nicardipine,
verapamil, metoclopramide, allopurinol, amiodarone,
and macrolide antibiotics (eg, erythromycin, azithromycin, clarithromycin), particularly in the elderly.3,64,66-70
Rifampin, phenytoin, phenobarbital, and carbamazepine
are P-450 accelerants that reduce CSA serum levels via
increased hepatic metabolism.3,66,67
Metronidazole
Metronidazole (MTZ) is a moderate inhibitor of CYP3A4
substrates that can increase levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (eg, simvastatin),
sildenal (Viagra, Pzer), and calcium channel blockers
(Table 7).71 MTZ also potentiates warfarin, thereby prolonging INR.3,55 Increased metabolism of MTZ (ie, elimination) occurs with coadministration of phenytoin and
phenobarbital; cimetidine increases the half-life, thereby
reducing MTZ clearance; and MTZ induces lithium toxicity even if a previous lithium level was stable. Alcohol
induces an antabuse71 (disulram) reaction; neuropathy is
common and worsened in the elderly.3,71
Ciprooxacin
Ciprooxacin72 decreases theophylline clearance with the
potential for a central nervous system adverse reaction

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Table 6. Cyclosporine Drug Interactions

Drug
Cyclosporine

Potentiate Renal
Dysfunction

Cyclosporine
Levels

Cyclosporine
Levels

Antibiotics:
ciprooxacin
gentamicin
tobramycin
vancomycin
trimethoprim/
sulfamethoxazole

Calcium channel
blockers:
diltiazem
nicardipine
verapamil

Antibiotics:
nafcillin
rifampin

Antineoplastic:
melphalan
Antifungals:
amphotericin B
ketoconazole
Anti-inammatory
drugs:
azapropazone
colchicine
diclofenac
naproxen
sulindac
Histamine-2 blockers:
cimetidine
ranitidine
Immunosuppressant:
tacrolimus
Fibric acid derivative:
fenobrate

Anticonvulsants:
carbamazepine
phenobarbital
phenytoin

Antifungals:
uconazole
itraconazole
ketoconazole

St. Johns Wort:

decreases serum
concentrations of
cyclosporine, resulting
in subtherapeutic levels

Antibiotics:
azithromycin
clarithromycin
erythromycin
quinupristin/
dalfopristin
Glucocorticosteroid:
methylprednisolone
Protease inhibitors:
indinavir
nelnavir
ritonavir
saquinavir

Other drugs:
octreotide
orlistat
sulnpyrazone
terbinane
ticlopidine

Other Interactions
Rifabutin: increases the
metabolism of drugs
metabolized by the
cytochrome P-450 system
Diclofenac: doubling of
blood levels and (reversible)
decrease in renal function
Methotrexate: concentrations were increased 30%
and the concentrations of
its metabolite, 7-hydroxy
methotrexate, were decreased
by approximately 80%. The
clinical signicance is not
known.
Decreased clearance of:
digoxin
colchicines
prednisolone
3-hydroxy-3-methyl-glutarylCoA reductase inhibitors
(eg, simvastatin, lovastatin)
Potentiate hyperkalemia
with:
potassium-sparing diuretics
angiotensin-converting
enzyme inhibitors
angiotensin II receptor
blockers

Other drugs:
allopurinol
amiodarone
bromocriptine
colchicine
danazol
imatinib
metoclopramide
oral contraceptives
Food:
grapefruit juice
increases absorption

(Table 8).73 Ciprooxacin also reduces caeine clearance,74 alters phenytoin concentrations in serum,3 and
enhances warfarin sodium levels, requiring meticulous
coagulation surveillance.74,75
Biologic Therapy
Anti-tumor necrosis factor antibodies76 are distributed
in the vascular compartment with a very slow half-life
of 914 days (Table 9). Age is not known to have an
eect, but a larger number of adverse eects are expected
with comorbidities such as CHF, hepatitis, bone mar-

row depression, and/or infection. Concurrent usage

with anakinra (Kineret, Amgen) and etanercept (Enbrel,
Immunex) may increase the risk of serious infections,
and potassium-sparing diuretics, live vaccines, and steroids should be avoided. Related hypocholesterolemic
seizures are additional concerns.76-78
Caveats
The basic principles when prescribing for elderly patients
involve recognition of the drug type, elimination patterns,
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Table 7. Metronidazole Drug Interactions

Drug
Metronidazole

Cytochrome
Association

Levels of CYP3A4
Substrates

Inhibits CYP:
3A4 (moderate)
2C9 (weak)

benzodiazepines
calcium channel blockers
cyclosporine
mirtazapine
nateglinide
nefazodone
sildenal (and other
phosphodiesterase type 5
inhibitors)
tacrolimus
venlafaxine
cisapride
ergot alkaloids
3-hydroxy-3-methyl-glutarylCoA reductase inhibitors
(lovastatin, simvastatin)
pimozide

Other Drug-Drug Interaction

Renal Impairment

Cimetidine: increase levels of

metronidazole
Cisapride: proarrhythmic due
to inhibition of metabolism
Ethanol: disulram-like
reactions
Lithium: may increase lithium
levels/toxicity
Phenytoin, phenobarbital:
may increase metabolism of
metronidazole
Warfarin: increases
prothrombin time prolongation

Inconsistent
recommendations;
consider dosage
reduction in longerterm therapy with
severe renal failure
(CrCl <10 mL/
minute)

CrCl=creatinine clearance.

Table 8. Ciprofloxacin Drug Interactions

Drug
Ciprooxacin

Cytochrome
Association

Levels/Eects of
CYP1A2 Substrates

Inhibits CYP:
1A2 (strong)
3A4 (weak)

aminophylline
uvoxamine
mexiletine
mirtazapine
ropinirole
tizanidine
triuoperazine

Drug-Drug Interaction
Caeine: may decrease caeine metabolism
Foscarnet: associated with an increased risk of
seizures
Glyburide: may increase therapeutic eects
Methotrexate: may decrease renal secretion
NSAIDs: risk of seizures may be increased
Phenytoin: may decrease levels
Probenecid: concurrent usage may decrease renal
excretion
Sevelamer: may decrease oral absorption
Theophylline: levels may increase
Tizanidine: levels may increasecontraindicated
Warfarin: anticoagulant eect may be enhanced
Metal cautions (aluminum, calcium, iron,
magnesium, and zinc): bind quinolones in the
gastrointestinal tract and inhibit absorption

NSAIDS=nonsteroidal anti-inflammatory drugs.

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Renal
Impairment
Caution
warranted with
renal impairment
dosage
adjustment
required

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Table 9.

Biologic Drug Interactions

Cytochrome
Association

Renal
Impairment

Hepatic
Impairment

Abciximab: increases potential for hypersensitivity reaction;

may increase risk of thrombocytopenia and/or reduced
therapeutic ecacy
Anakinra: may increase risk of serious infection when used
in combination
Etanercept: may increase risk of serious infection when used
in combination
Vaccine (dead organism): iniximab may decrease the eect
of vaccines
Vaccine (live organism): immunosuppressants may enhance
the adverse/toxic eects of vaccines

No

No

No

Adalimumab

Anakinra: increases risk of serious infection and

neutropenia
Methotrexate: reduces adalimumab clearance
Vaccine (live organism): immunosuppressants may enhance
the adverse/toxic eects of vaccines

No

No

No

Natalizumab

Caution with concurrent immunomodulator

therapy/immunosuppression/antineoplastic therapy, as
they may be risk factors for the development of PML,
opportunistic infections, and neoplasms

No

Not studied

Postmarketing
reports of
hepatotoxicity

Drug

Drug-Drug Interaction

Iniximab

Interferon beta-1a: may increase the levels of natalizumab;

no dosage adjustment necessary
Caution advised in patients with history of depression
Caution advised with hepatotoxic drugs, as they can increase
bilirubin and transaminases
PML=progressive multifocal leukoencephalopathy.

drug metabolism enzymes, and GFR eects. Most drugs

require metabolic processing prior to elimination, as with
hepatic elimination in the younger IBD patient and in the
t elderly population. An age-dependent decline occurs
in GFR, but to a lesser degree in the latter population.
Caution is required when using antidiarrheals,
analgesics, or opioids, as these agents may be less eective due to higher endogenous opioid levels.79 Therefore,
there is an inherent but faulty tendency to push dosage
with adverse events such as confusion, ileus, or impaction. Anticholinergics should be avoided because of
side eects associated with urinary retention, glaucoma,
confusion, or arrhythmias, which are particularly problematic in the elderly.
Frailty may be more important than age in drug
elimination. Therefore, a safe principle is start low; go
slow when initiating any drug in this population.

Osteoporosis
The fracture rate is higher in the elderly population and
associated with an additive drug eect (GCS, MTX,
CSA) to the disease impact with an increase of inammatory cytokines. Coexistent malabsorption (vitamin D,
calcium) is often overlooked (85% of hospitalized elderly
patients are protein malnourished).43 Twenty-one percent of hospitalized seniors take in less than 50% of their
calculated maintenance nutritional requirements.42
Summary
In conclusion, it is important to recognize the impending
burden of baby boomers on healthcare, which will create
new standards for the allocation of available resources.
The present concepts of the immutability of genetic

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K AT Z A N D F E L D S T E I N

predisposition to disease by the aging eect should be

challenged. Physicians should examine questions such as,
Does the diagnosis or the character of the disease change
with time? This change is seen in UC conversion to CD
and altered severity with aging. It is essential to distinguish between the t elderly and frail elderly when
designing clinical trials, studying pharmacokinetics, and
evaluating data. Another important issue is to establish
a cadre of clinician-investigators skilled in the biology of
aging (ie, drug interactions and comorbid disease impact),
with the goal of saving lives in addition to saving money.
One current approach to drug therapy in the elderly is to
start low; go slow and then reassess their candidacy for
more aggressive therapy (biologics, apheresis, surgery) and
not treat or exclude patients on the basis of age alone.
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